Cis-platin, carbo-platin and oxaliplatin are called 1st, 2nd and 3rd generation of platinum based anticancer drugs respectively. The 1st generation drug Cis-platin is efficacious in many human cancer cell-lines but suffers from the disadvantage of less internalization (thus more doses are needed) and more toxicity issues. The 2nd generation drug carboplatin is shown to be accumulated more amount in nucleus than cis-platin due to more internalization but still shows cross-resistance with some of the cis-platin resistant tumors due to the hydrolysis of amino groups after DNA cross linking and also due to the easy recognition of diammineplatinum fragment by DNA repair enzymes. (Ref. Cancer Therapy, 2007, Vol 5, 537-583).

The cellular and molecular aspects of the mechanism of action of the 3rd generation drug oxaliplatin have not yet been fully elucidated. However, the intrinsic chemical and steric characteristics of the non-hydrolyzable and hydrophobic diaminocyclohexane (DACH)-platinum adducts on DNA appear to contribute to the lack of cross-resistance with cisplatin and carboplatin. It has been shown recently that attachment of lipids to the cisplatin and oxaliplatin backbone reduces the toxicity of the drugs to a significant extent by formation of nano-particle (EPR effect). (PNAS, 2012, vol. 109, 11294-11299).
The use of nanotechnology in cancer is emerging globally. Although there are few reports on nanoparticles in cancer therapy but all have various drawbacks such as toxicity, low release kinetics of drug, low circulation stability and so on.
Lipid-containing nanoparticles (e.g. Doxil, a pegylated liposomal formulation of doxorubicin hydrochloride) and albumin-complexes (e.g. Abraxane, a paclitaxel-albumin complex) nanoparticles are used in humans and have been demonstrated as having improved systemic toxicity profile and have helped resolve certain formulation challenges (Ferrari M, Nature Rev. Cancer, 2005, 5:161). Platinum-based chemotherapeutic agents are used as first line of therapy in over 70% of all cancers. Cisplatin undergoes rapid formation of cis-[Pt(NH3)2Cl(OH2)]+ and cis-[Pt(NH3)2(OH2)]2+ resulting in nephrotoxicity. Further, aquation of both carboplatin and oxaliplatin are significantly slower, resulting in decreased potency. In the recent past, considerable progress has been made wherein, Dhar et al (PNAS, 2008, 105, 17356) generated a platinum (IV) complex (c,t,c-[Pt(NH3)2(O2CCH2CH2CH2CH2CH3)2Cl2] that is hydrophobic enough for encapsulation into PLGA-b-PEG nanoparticles. However, the prodrug in this case has to be intracellularly processed into cisplatin. Furthermore, alternative strategies based on conjugation of platinum to polymers (eg a polyamidoamine dendrimer-platinum complex) resulted in a 200-550 fold reduction in cytotoxicity than free cisplatin. This was a result of strong bonds formed between the polymer and platinum (J Pharm Sci, 2009, 98, 2299). Another example is AP5280, a N-(2-hydroxypropyl) methacrylamide copolymer-bound platinum that is less potent than carboplatin. Here, the platinum is held by an aminomalonic acid chelating agent coupled to the COOH-terminal glycine of a tetrapeptide spacer (Clin Can Res, 2004, 10, 3386; Eur J Can, 2004, 40, 291).
Further, WO 2010/091192 A2 (Sengupta et al.) discloses biocompatible conjugated polymer nanoparticles including a copolymer backbone, a plurality of sidechains covalently linked to said backbone, and a plurality of platinum compounds dissociably linked to said backbone. The disclosure is further directed to dicarbonyl-lipid compounds wherein a platinum compound is dissociably linked to the dicarbonyl compound.
However, various drawbacks are associated with the presently employed platinum compounds and nanoparticles. The present disclosure aims at overcoming the drawbacks of the prior art and providing for stable, potent and safer platinum compounds and nano-platinates in cancer chemotherapy.